Long-Term Tamoxifen Therapy: An Appropriate Chemosuppressive Treatment for Breast Cancer

  • V. Craig Jordan
Conference paper
Part of the ESO Monographs book series (ESO MONOGRAPHS)


Tamoxifen (Nolvadex®) is a non-steroidal antioestrogen and the first-line endocrine therapy for breast cancer [1–3]. The drug has proved to have efficacy as an adjuvant in node-positive disease [3,4] and increasing numbers of node-negative breast cancer patients are being treated with tamoxifen [5]. A remarkable feature of treatment with tamoxifen is the low incidence of side effects [1,3]. These clinical observations and the large body of evidence from the laboratory [6,7] have focussed clinical attention on long-term, or indefinite (treatment until relapse), adjuvant tamoxifen therapy [5,8–10].


Estrogen Osteoporosis Adenocarcinoma Oncol Tamoxifen 


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  1. 1.
    Furr BJA, Jordan VC: The pharmacology and clinical uses of tamoxifen. Pharm Ther 1984 (25):127–205CrossRefGoogle Scholar
  2. 2.
    Jordan VC (ed) Estrogen/Antiestrogen Action and Breast Cancer Therapy. University of Wisconsin Press, Madison 1986Google Scholar
  3. 3.
    Love RR: Tamoxifen therapy in primary breast cancer: biology, efficacy and side effects. J Clin Oncol 1989 (7):803–815PubMedGoogle Scholar
  4. 4.
    Early Breast Cancer Trialists’ Collaborative Group: Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. N Engl J Med 1988(319):1681–1692CrossRefGoogle Scholar
  5. 5.
    Fisher B, Costantino J, Redmond C et al: A randomized clinical trial evaluating tamoxifen in the treatment of patients with node negative breast cancer who have estrogen receptor positive tumors. N Engl J Med 1989 (320):479–484PubMedCrossRefGoogle Scholar
  6. 6.
    Jordan VC: Laboratory studies to develop general principles for the treatment of breast cancer with antiestrogens: problems and potential for future clinical applications. Breast Cancer Res Treat 1983 (3 Suppl):s73–s86PubMedCrossRefGoogle Scholar
  7. 7.
    Jordan VC: Long-term tamoxifen therapy for breast cancer. In: DeVita VT, Hellman S, Rosenberg S (eds) Important Advances in Oncology. Lippincott, Philadelphia 1989 pp 179–192Google Scholar
  8. 8.
    Tormey DC, Jordan VC: Long-term tamoxifen adjuvant therapy in node-positive breast cancer: a metabolic and pilot clinical study. Breast Cancer Res Treat 1984 (4) :297–302PubMedCrossRefGoogle Scholar
  9. 9.
    Fisher B and other NSABP Investigators: Prolonging tamoxifen for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med 1987 (106):649–654PubMedGoogle Scholar
  10. 10.
    Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC): Adjuvant tamoxifen in the management of operable breast cancer: the Scottish trial. Lancet 1987 (ii):171–175Google Scholar
  11. 11.
    Love RR, Mazess RB, Tormey DC et al: Bone mineral density in women with breast cancer treated for at least two years with tamoxifen. Breast Cancer Res Treat 1988(12):297–301PubMedCrossRefGoogle Scholar
  12. 12.
    Turken S, Siris E, Seldin E et al: Effects of tamoxifen on spinal bone density in women with breast cancer. JNCI 1989 (91):1086–1088Google Scholar
  13. 13.
    Bertelli G, Pronzata P, Amaroso D et al: Adjuvant tamoxifen in primary breast cancer: influence on plasma lipids and antithrombin III levels. Breast Cancer Res Treat 1988 (12):307–310PubMedCrossRefGoogle Scholar
  14. 14.
    Antunes CM, Stolley PD, Rosenhein NB et al: Endometrial cancer and estrogen use: report of a large case-control study. N Engl J Med 1979 (300):9–13PubMedCrossRefGoogle Scholar
  15. 15.
    Weiss NS, Szekely DR, Austin DF: Increasing incidence of endometrial cancer in the United States. N Engl J Med 1976 (294):1259–1262PubMedCrossRefGoogle Scholar
  16. 16.
    Fox H: Endometrial carcinogenesis and its relation to ©estrogens. Path Res Pract 1984 (1979):13–19CrossRefGoogle Scholar
  17. 17.
    Whithead Ml, Fraser D: Controversies concerning the safety of estrogen replacement therapy. Am J Obstet Gynecol 1987 (156):1312–1322Google Scholar
  18. 18.
    Hillner BE, Hollenberg JP, Pauker SG: Postmenopausal estrogen in prevention of osteoporosis. Am J Med 1986 (80):1115–1127PubMedCrossRefGoogle Scholar
  19. 19.
    Henderson BE, Ross RK, Lobo RA, Pike MC, Mack TM: Re-evaluating the role of progestogen therapy after the menopause. Fert Steril 1988 (498 Suppl):9s–15sGoogle Scholar
  20. 20.
    Bergkvist L, Adami H-O, Persson I et al: The risk of breast cancer after estrogen and estrogen-progestin replacement. N Engl J Med 1989 (321)293–297PubMedCrossRefGoogle Scholar
  21. 21.
    Jordan VC, Robinson SP: Species-specific pharmacology of antiestrogens: role of metabolism. Fed Proc 1987 (46):1870–1874PubMedGoogle Scholar
  22. 22.
    Harper MJK, Walpole AL: A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J Reprod Fertil 1967 (13):101–119PubMedCrossRefGoogle Scholar
  23. 23.
    Broens J, Mouridsen HT, Soerensen HM: Tamoxifen in advanced endometrial carcinoma. Cancer Chemother Pharmacol 1980 (4):805–811CrossRefGoogle Scholar
  24. 24.
    Swenerton KD: Treatment of advanced endometrial adenocarcinoma with tamoxifen. Cancer Treat Rep 1980(64):805–811PubMedGoogle Scholar
  25. 25.
    Killackey MA, Hakes TB, Pierce VK: Endometrial adenocarcinoma in breast cancer patients receiving tamoxifen. Cancer Treat Rep 1985 (69):237–238PubMedGoogle Scholar
  26. 26.
    Hardell L: Tamoxifen as risk factor for carcinoma of corpus uteri. Lancet 1988 (ii):563CrossRefGoogle Scholar
  27. 27.
    Hardell L: Pelvic irradiation and tamoxifen as risk factors for carcinoma of corpus uteri. Lancet 1988 (il):1432CrossRefGoogle Scholar
  28. 28.
    Fornander T, Rutqvist LE, Cedermark B et al: Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1989 (l):117–120CrossRefGoogle Scholar
  29. 29.
    Satyaswaroop PG, Zaino RJ, Mortel R: Estrogen-like effect of tamoxifen on human endometrial carcinoma transplanted into nude mice. Cancer Res 1984 (44):4006–4010PubMedGoogle Scholar
  30. 30.
    Clark CL, Satyaswaroop PG: Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma. Cancer Res 1985 (45):5417–5420Google Scholar
  31. 31.
    Gottardis MM, Robinson SP, Satyaswaroop PG, Jordan VC: Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Res 1988 (48):812–815PubMedGoogle Scholar
  32. 32.
    Mouridsen HT, Ellemann K, Mattsson W et al: Therapeutic effect of tamoxifen versus tamoxifen combined with medroxyprogesterone acetate in advanced breast cancer in postmenopausal women. Cancer Treat Rep 1979 (63):171 -175PubMedGoogle Scholar
  33. 33.
    Jabara AG, Toyens PH, Harcourt AG: Effects of time and duration of progesterone administration on mammary tumors induced by 7,12-dimethylbenz(a)-anthracene in Sprague Dawley rats. Br J Cancer 1973(27):63–71PubMedCrossRefGoogle Scholar
  34. 34.
    Robinson SP, Jordan VC: Reversal of the antitumour effects of tamoxifen by progesterone in the 7, 12-dimethylbenzanthracene-induced rat mammary carcinoma model. Cancer Res 1987 (47):5386–5390PubMedGoogle Scholar
  35. 35.
    Robinson SP, Mauel DA, Jordan VC: Antitumour actions of toremifene in the 7,12-dimethylbenzanthracene (DMBA)-induced rat mammary tumor model. Eur J Cancer Clin Oncol 1988(24):1817–1821PubMedCrossRefGoogle Scholar
  36. 36.
    Gottardls MM, Jordan VC: Development of tamoxjfen-stimulated growth of MCF-7 tumors in athymlc mice after long-term antiestrogen administration. Cancer Res 1988 (48):5183–5187Google Scholar
  37. 37.
    Osborne CK, Coronado EB, Robinson JP: Human breast cancer in the athymic nude mouse: cytostatic effects of long-term antioestrogen therapy. Eur J Cancer Clin Oncol 1987 (23):1189–1196PubMedCrossRefGoogle Scholar
  38. 38.
    Gottardis MM, Wagner RJ, Borden EC, Jordan VC: Differential ability of antiestrogens to stimulate breast cancer cell (MCF-7) growth in vivo and in vitro. Cancer Res 1989 (49):4765–4769PubMedGoogle Scholar
  39. 39.
    Gottardis MM, Jiang SY, Jeng MH, Jordan VC: Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Res 1989 (49):4090–4093PubMedGoogle Scholar
  40. 40.
    Murray RML, Pitt P: Aminoglutethimide in tamoxifen-resistant patients: the Melbourne experience. Cancer Res 1982 (42 Suppl):3437s–3441sPubMedGoogle Scholar
  41. 41.
    Wakeling AE, Bowler J: Steroidal pure antioestrogens. J Endocrinol 1987 (112):R7–R10PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • V. Craig Jordan
    • 1
  1. 1.Department of Human OncologyUniversity of Wisconsin Clinical Cancer CenterMadisonUSA

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